Monthly Archives: August 2017

Aclaris Therapeutics, Confluence Life Sciences, Neal Walker, Soft JAK Inhibitors

Aclaris Therapeutics and Dr. Neal Walker Update

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Aclaris Therapeutics has been in the news a lot so far this month. The company has gone overboard with press releases and e-mail alerts (if you are subscribed) during the first two weeks of August. When I read all their recent press releases, I saw very little in the way of their topical JAK inhibitor program for male pattern hair loss, although one reader e-mailed me about one particular sentence in this press release in which they state that they will:

“Continue to develop another series of topical JAK inhibitors for the treatment of androgenetic alopecia (AGA)”.

Also of major interest is their recent purchase of Confluence Life Sciences.

However, something else extremely significant that I totally missed (despite my weekly Google Alerts about the company) was sent to me by a blog reader yesterday. It is a 10-page Seeking Alpha earnings call/interview with Aclaris CEO Neal Walker and others (can only be viewed in its entirety after registration). There are numerous interesting points in those 10 pages, but by far the most important for our purposes are the below two quotes from the CEO:

Mr. Walker: “We view the soft JAK as applicable to things like male-female pattern baldness”.

Shorty thereafter…

Mr Lugo: “Understood. What’s the timing for the soft JAK program entering the clinic? I’m not sure I heard that”.

Mr. Walker: “We will be giving a more full guidance on that at our Investor Day. We’re looking at approximately 2 years for some of our pipeline assets“.

My Thoughts

  • It seems like they are classifying “topical covalently bound JAK inhibitors” as “soft JAK inhibitors”.
  • Their collaboration and subsequent takeover of Confluence Life Sciences involves soft JAK inhibitor technology among other things. Mr. Walker points out elsewhere in the interview that their original reason for collaboration with Confluence entailed the latter’s soft JAK inhibitor technology.
  • I presume that Mr. Lugo’s comment about “entering the clinic” means being in use at clinics. It seems very hard to imagine that this can happen in two years as Mr. Walker seems to imply. Aclaris’ pipeline currently has both its hair loss related topical JAK inhibitors in pre-clinical trials. The only way they could get these to the clinic in two years is if somehow the US FDA has significantly less stringent regulations for topical versions of drugs relative to oral versions of the same drugs (especially if the oral version has already been approved or is in final phase 3 trials in two years).

So the JAK hope-train continues even if commentator “nasa_rs” is missing lately:-)

JAK-STAT, Lactate, RCGD423, UK5099

UCLA vs USC in the Hair Loss World

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University of California Los Angeles (UCLA) and University of Southern California (USC) are both based in Los Angeles, California in the USA. They have one of the most intense and historic rivalries in American college sports, especially in American football. The two campuses are separated by just 12 miles. In an amazing coincidence, the two most important hair loss research related discoveries in the world this month came out of these very two universities.

UCLA scientists find two new ways to activate hair follicle stem cells

For our purposes, the UCLA findings (published just today) seem to have the greatest significance. Scientists (led by Heather Christofk and William Lowry) have found two drugs that activate hair follicle stem cells in mice. Interestingly, both drugs are topical, and one (RCGD423) involves activating the JAK-STAT signaling pathway. No idea if this drug is connected to JAK inhibitors in any way, but that acronym keeps coming up regularly these days.

Both drugs involve increasing lactate production. Apparently, lactate production is strongly connected to hair follicle stem cell activation and hair cycling. In their initial research, the UCLA scientists blocked lactate production genetically in mice and found that this prevented hair follicle stem cell activation. Thereafter, they found that increasing lactate production genetically in mice accelerated hair follicle stem cell activation and increased the hair cycle.

RCGD423

The first drug, RCGD423, activates the JAK-STAT signaling pathway, which in turn leads to an increase in the production of lactate. This then activates hair follicle stem cells and also leads to quicker hair growth. UCLA holds the original patent for RCGD423, related to its ability to rejuvenate cartilage, and has filed a provisional patent for its use for hair growth purposes.

UK5099

The second drug, UK5099, blocks pyruvate (a glucose metabolite) from entering cell mitochondria. Interestingly, this forces an increase in the production of lactate in the hair follicle stem cells and therefore accelerates hair growth. UCLA has filed a provisional patent for using UK5099 for hair growth purposes.

Perhaps the most interesting quote from the earlier linked article summarizing these findings is: “I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general“. On this blog, I have covered the connection between fat cells (adipose tissue) and hair growth numerous times due to significant recent research in that area. So I am not surprised at all that metabolism is also important when it comes to hair growth.

It is, however, surprising that hair loss research has uncovered so many new distinct pathways and mechanisms in the past few years. All of these are unrelated to the tried and tested method of targeting dihydrotestosterone (DHT) reduction. This is great news, since we already know that even close to 100 percent reduction in DHT will not bring back long-lost hair for most people, plus often comes with side effects.

USC scientists restore hair generation in defunct adult cells

A team of scientists from USC (led by Dr. Mingxing Lei, with collaboration from others in China and the UK) have managed to restore hair regeneration properties in adult mice cells that had stopped growing hair. A non-scientist friendlier summary of this work can be found here. One of the co-authors of this paper is Dr. Cheng-Ming Chuong, who I covered on this blog before.

Using intensive video analysis and documentation, bioinformatics, and molecular screenings, the scientists figured out a:

Molecular “how to” guide for driving individual skin cells to self-organize into organoids that can produce hair.

Also:

In the future, this work can inspire a strategy for stimulating hair growth in patients with conditions ranging from alopecia to baldness.

Very unlikely to come to fruition anytime soon of course, but considering that some of the research collaborators are from China… perhaps things may move faster than I am guessing if they could shift their research and potential clinical trials to that country?